J Obstet Gynaecol Res. 2017 Apr;43(4):736-743.

Increased ipsilateral uterine artery vascular resistance in women with ovarian endometrioma.

Waratani M1Mori T1Ito F1Tanaka Y1Koshiba A1Takahata A2Kitawaki J1.

 

Abstract

AIM:

The aim of this study was to elucidate whether the presence of an ovarian endometrioma is associated with impaired vascular flow. We investigated changes in vascular flow on the ipsilateral and contralateral side of the endometrioma, before and after surgery.

METHODS:

This prospective case-control study included 144 women (ovarian endometrioma [n = 40], endometriosis without ovarian endometrioma [n = 33], non-endometriotic ovarian cyst [n = 17], and normal pelvis [n = 54]). The uterine artery (UtA) vascular resistance indices (pulsatility index [PI] and resistance index [RI]) were measured using transvaginal Doppler sonography, and UtA diameters were measured using magnetic resonance imaging.

RESULTS:

The UtA PI and RI were significantly higher on the ipsilateral side of the endometrioma than on the contralateral unaffected side in the endometrioma group (P < 0.01), as well as in the non-endometriotic ovarian cyst group (P < 0.05), and normal pelvis group (P < 0.01). The UtA PI and RI on the ipsilateral side of the endometrioma were significantly lower after cystectomy than before cystectomy (P < 0.01). The UtA diameters were significantly larger (P < 0.01) on the ipsilateral side of the endometrioma than on the contralateral side.

CONCLUSION:

The UtA-vascular resistance might be higher on the ipsilateral side of the endometrioma than on the contralateral unaffected side, indicating a risk of subclinical atherosclerosis in women with endometriosis.

 

 

Fertil Steril. 2017 Mar;107(3):533-536.

Progestin-only pills may be a better first-line treatment for endometriosis than combined estrogen-progestin contraceptive pills.

Casper RF1.

 

Abstract

For decades, combined estrogen-progestin oral contraceptive pills (OCPs) have been the first-line treatment for menstrual and pelvic pain associated with endometriosis without any clinical evidence of efficacy. Initial relief provided by OCPs is likely a result of improvement in primary dysmenorrhea. Biologic data and limited clinical evidence support a potential adverse effect of long-term use of OCPs on the progression of endometriosis. In contrast, there is randomized, controlled trial data to support the use of oral progestin-only treatment for pelvic pain associated with endometriosis and for suppressing the anatomic extent of endometriotic lesions. Both norethindrone acetate and dienogest have regulatory approval for treating endometriosis and may be better than OCPs as a first-line therapy.

 

 

Acta Obstet Gynecol Scand. 2017 Jun;96(6):694-701

Efficacy, safety and tolerability of the CCR1 antagonist BAY 86-5047 for the treatment of endometriosis-associated pelvic pain: a randomized controlled trial.

Trummer D1Walzer A2Groettrup-Wolfers E3Schmitz H2.

 

Abstract

INTRODUCTION:

Antagonism of CC chemokine receptor type 1 (CCR1) may provide a novel treatment approach for women with symptomatic endometriosis. Studies of CCR1 antagonists in these patients have not been reported.

MATERIAL AND METHODS:

Women (n = 110; 18-45 years) with symptomatic endometriosis were randomized to BAY 86-5047 or placebo for 12 weeks. Pelvic pain was assessed using the visual analogue scale (VAS) and women recorded the intake of pain medication in a diary. The primary efficacy outcome was a composite of the absolute change in VAS score and the cumulative change in consumption of analgesics between baseline and the end of treatment. Safety assessments included adverse events, blood and urine evaluation and electrocardiography.

RESULTS:

Mean VAS scores decreased from 64.8 mm at baseline to 49.2 mm at week 12 in the BAY 86-5047 group and from 67.2 mm to 47.8 mm in the placebo group. The proportion of women using analgesics decreased from 33.9% to 11.5% or from 44.4% to 15.4% for patients who received BAY 86-5047 or placebo, respectively. There was no significant difference between the two treatment groups in terms of change in VAS scores (p = 0.45) or intake of analgesics (p = 0.82). A three-step sensitivity analysis failed to show superiority of BAY 86-5047 over placebo (p = 0.67). BAY 86-5047 was well tolerated and no significant safety concerns arose during the study.

CONCLUSIONS:

Based on these results, BAY 86-5047 is unlikely to be useful in the treatment of women with endometriosis-associated pelvic pain.

 

 

Hum Mol Genet. 2016 Nov 15;25(22):5046-5058.

Endometriosis risk alleles at 1p36.12 act through inverse regulation of CDC42 and LINC00339.

Powell JE1,2Fung JN3Shakhbazov K1Sapkota Y3Cloonan N3Hemani G1,4Hillman KM3Kaufmann S3Luong HT3Bowdler L3Painter JN3Holdsworth-Carson SJ5Visscher PM1Dinger ME6,7Healey M5Nyholt DR3,8French JD3Edwards SL3Rogers PA5Montgomery GW3.

 

Abstract

Genome-wide association studies (GWAS) have identified markers within the WNT4 region on chromosome 1p36.12 showing consistent and strong association with increasing endometriosis risk. Fine mapping using sequence and imputed genotype data has revealed strong candidates for the causal SNPs within these critical regions; however, the molecular pathogenesis of these SNPs is currently unknown. We used gene expression data collected from whole blood from 862 individuals and endometrial tissue from 136 individuals from independent populations of European descent to examine the mechanism underlying endometriosis susceptibility. Association mapping results from 7,090 individuals (2,594 cases and 4,496 controls) supported rs3820282 as the SNP with the strongest association for endometriosis risk (P = 1.84 × 10−5, OR = 1.244 (1.126-1.375)). SNP rs3820282 is a significant eQTL in whole blood decreasing expression of LINC00339 (also known as HSPC157) and increasing expression of CDC42 (P = 2.0 ×10−54 and 4.5×10−4 respectively). The largest effects were for two LINC00339 probes (P = 2.0 ×10−54; 1.0 × 10−34). The eQTL for LINC00339 was also observed in endometrial tissue (P = 2.4 ×10−8) with the same direction of effect for both whole blood and endometrial tissue. There was no evidence for eQTL effects for WNT4. Chromatin conformation capture provides evidence for risk SNPs interacting with the promoters of both LINC00339 and CDC4 and luciferase reporter assays suggest the risk SNP rs12038474 is located in a transcriptional silencer for CDC42 and the risk allele increases expression of CDC42. However, no effect of rs3820282 was observed in the LINC00339 expression in Ishikawa cells. Taken together, our results suggest that SNPs increasing endometriosis risk in this region act through CDC42, but further functional studies are required to rule out inverse regulation of both LINC00339 and CDC42.

 

 

 

 

Reprod Sci. 2017 Oct;24(10):1469-1475.

Ultrastructural Evaluation of Eutopic Endometrium of Infertile Women With and Without Endometriosis During the Window of Implantation.

Da Broi MG1Rocha CV Jr1Carvalho FM2Martins WP1Ferriani RA1Navarro PA1,3.

 

Abstract

Endometriosis is frequently associated with infertility and it is believed that the impairment of endometrial receptivity may be one of the mechanisms involved in this condition. Pinopodes are endometrial cycle-dependent structures that seem to participate in embryo implantation, and alterations in their presence and/or morphology during the window of implantation could affect the endometrial receptivity and be involved in the disease-related infertility. However, the data on pinopodes in these women are scarce and inconclusive. This pilot study aimed to evaluate the cell pattern, including the presence and developmental stage of pinopodes, in eutopic endometrium of infertile patients with and without endometriosis during the window of implantation, using scanning electron microscopy (SEM). Endometrial biopsies were performed using a Pipelle catheter, and 12 samples classified in the window of implantation (6 infertile women with endometriosis and 6 infertile controls) were analyzed by SEM. The frequencies of cell types (microvilli, ciliated, and pinopodes) and the developmental stage of pinopodes were compared between groups using Mann-Whitney U test. Although the study was limited by its sample size, no large differences were detected between the groups regarding the presence and developmental stage of pinopodes, suggesting the absence of large structural changes in the endometrium of infertile women with endometriosis during the window of implantation.

 

 

Clin Proteomics. 2017 Feb 2;14:7

Cervical mucus proteome in endometriosis.

Grande G1Vincenzoni F2Milardi D1Pompa G1Ricciardi D3Fruscella E1Mancini F1Pontecorvi A4Castagnola M2Marana R1,3.

 

Abstract

BACKGROUND:

Endometriosis is a chronic gynecological inflammatory disease characterized by the presence of functional endometrial glands and stroma outside of the uterine cavity. It affects 7-10% of women of reproductive age and up to 50% of women with infertility. The current gold standard for the diagnosis combines laparoscopic evaluation and biopsy of the visualized lesions. However, laparoscopy requires general anesthesia and developed surgical skills and it has a high procedural cost. In addition, it is associated with the risk, although rare, of potential intraoperative or postoperative complications. To date, several noninvasive biomarkers have been proposed; however, no definite diagnostic biomarker is yet available. The aim of this study was to characterize the CM proteome in patients with endometriosis using high resolution mass spectrometry-based proteomics, implemented by bioinformatic tools for quantitative analysis, in order to investigate the pathophysiological mechanisms of endometriosis.

METHODS:

Cervical mucus samples were collected from patients affected by endometriosis and fertile controls. An aliquot of the soluble acidic fraction of each cervical mucus sample, corresponding to 0.5 mg of total protein, was left to digest with sequencing grade modified porcine trypsin. The peptides were analyzed by LC-MS/MS on a high resolution Orbitrap Elite mass spectrometer and data were evaluated using bioinformatic tools.

RESULTS:

We aimed at the first total profiling of the cervical mucus proteome in endometriosis. From the list of identified proteins, we detected a number of differentially expressed proteins, including some functionally significant proteins. Six proteins were quantitatively increased in endometriosis, almost all being involved in the inflammatory pattern. Nine proteins were quantitatively reduced in endometriosis, including some proteins related with local innate immunity (CRISP-3 and Pglyrp1) and protection against oxidative stress (HSPB1). Fifteen proteins were not detected in endometriosis samples including certain proteins involved in antimicrobial activity (SLURP1 and KLK13) and related to seminal plasma liquefaction and male fertility (KLK13).

CONCLUSIONS:

This is the first application of high resolution mass spectrometry-based proteomics aimed in detecting an array of proteins in CM to be proposed for the noninvasive diagnosis of endometriosis. This chronic disease presents in CM an inflammatory protein pattern.

 

 

Rom J Morphol Embryol. 2016;57(4):1337-1341.

The experience of our Clinic in laparoscopy for adnexal masses and the correlation between ultrasound findings and pathological results.

Pleş L1Sima RMBurnei AAlbu DFBujor MAConci STeodorescu VEdu A.

 

Abstract

INTRODUCTION:

An adnexal mass (mass of the ovary, Fallopian tube, or surrounding connective tissues) is a common gynecological problem. Ovarian pathology can occur at any time from fetal life to menopause. Sonography is a clinically important imaging modality for assessing whether an adnexal mass is likely benign or possibly malignant. Most ovarian surgeries are for benign disease and can be performed laparoscopically.

PATIENTS, MATERIALS AND METHODS:

We retrospectively evaluated all the patients from our Clinic who underwent laparoscopy for adnexal tumors in the last three year. We were studying the correlation of the preoperative ultrasound examination and the pathological result for each case.

RESULTS:

In this study, there were included 71 patients who underwent a laparoscopic intervention for adnexal tumors. The average age was 33 years old (range 18 and 60 years old). The ultrasound findings were ovarian endometriosis in 23.9% of cases, left ovarian cysts (22.5%) and right ovarian tumors (18.3%), and the lowest percentage was of left ovarian tumors (8.5%). Regarding the histopathological examination, we found the following results: ovarian endometriosis (32.4%), ovarian functional cysts (15.5%), serous ovarian cysts (15.5%), salpingitis (12.7%), ovarian myoma (7%), papillary serous ovarian cysts (4.2%), ovarian teratoma cysts (9.9%), one case (1.4%) of ovarian carcinoma and one case (1.4%) of borderline serous tumor. In this study, we observed that it was a strong correlation between the ultrasound finding and the pathological result for adnexal tumors (p<0.001).

CONCLUSIONS:

The laparoscopy was performed in our Clinic for adnexal masses with benign characters in ultrasound examination. The histopathological examination confirmed the diagnosis, being only one case of ovarian carcinoma in this study.

 

 

Hum Reprod. 2017 Apr 1;32(4):893-904.

The genetic regulation of transcription in human endometrial tissue.

Fung JN1,2Girling JE3Lukowski SW1Sapkota Y2,4Wallace L1Holdsworth-Carson SJ3Henders AK1Healey M3Rogers PAW3Powell JE1Montgomery GW1,2.

 

Abstract

STUDY QUESTION:

Do genetic effects regulate gene expression in human endometrium?

SUMMARY ANSWER:

This study demonstrated strong genetic effects on endometrial gene expression and some evidence for genetic regulation of gene expression in a menstrual cycle stage-specific manner.

WHAT IS KNOWN ALREADY:

Genetic effects on expression levels for many genes are tissue specific. Endometrial gene expression varies across menstrual cycle stages and between individuals, but there are limited data on genetic control of expression in endometrium.

STUDY DESIGN, SIZE, DURATION:

We analysed genome-wide genotype and gene expression data to map cis expression quantitative trait loci (eQTL) in endometrium.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

We recruited 123 women of European ancestry. DNA samples from blood were genotyped on Illumina HumanCoreExome chips. Total RNA was extracted from endometrial tissues. Whole-transcriptome profiles were characterized using Illumina Human HT-12 v4.0 Expression Beadchips. We performed eQTL mapping with ~8 000 000 genotyped and imputed single nucleotide polymorphisms (SNPs) and 12 329 genes.

MAIN RESULTS AND THE ROLE OF CHANCE:

We identified a total of 18 595 cis SNP-probe associations at a study-wide level of significance (P < 1 × 10-7), which correspond to independent eQTLs for 198 unique genes. The eQTLs with the largest effect in endometrial tissue were rs4902335 for CHURC1 (P = 1.05 × 10-32) and rs147253019 for ZP3 (P = 8.22 × 10-30). We further performed a context-specific eQTL analysis to investigate if genetic effects on gene expression regulation act in a menstrual cycle-specific manner. Interestingly, five cis-eQTLs were identified with a significant stage-by-genotype interaction. The strongest stage interaction was the eQTL for C10ORF33 (PYROXD2) with SNP rs2296438 (P = 2.0 × 10-4), where we observe a 2-fold difference in the average expression levels of heterozygous samples depending on the stage of the menstrual cycle.

LARGE SCALE DATA:

The summary eQTL results are publicly available to browse or download.

LIMITATIONS, REASONS FOR CAUTION:

A limitation of the present study was the relatively modest sample size. It was not powered to identify trans-eQTLs and larger sample sizes will also be needed to provide better power to detect cis-eQTLs and cycle stage-specific effects, given the substantial changes in expression across the menstrual cycle for many genes.

WIDER IMPLICATIONS OF THE FINDINGS:

Identification of endometrial eQTLs provides a platform for better understanding genetic effects on endometriosis risk and other endometrial-related pathologies.

 

 

 

Cancer Control. 2017 Jan;24(1):83-88.

Endometriosis Mimicking Soft-Tissue Neoplasms: A Potential Diagnostic Pitfall.

Ding Y1Gibbs J2Xiong G3Guo S4Raj S5Bui MM6.

 

Abstract

Endometriosis is a common gynecological disorder most often involving the pelvic region. Although it is rare, endometriosis occurring outside of the peritoneal cavity most commonly occurs within scars of the abdominal wall, but it has been reported in the lungs, pleura, kidneys, brain, and the extremities. Herein, we present 2 cases of endometriosis, including 1 case of endometriosis of the wrist that clinically mimicked a soft-tissue neoplasm and 1 case of right-groin endometriosis mimicking synovial sarcoma during the initial pathological interpretation of findings on fine needle aspiration. We also report on a third patient with synovial sarcoma to demonstrate a diagnostic pitfall. To our knowledge, endometriosis within the skeletal muscle of the wrist has not been previously reported in the literature. A literature review was performed, and we discuss how this diagnostic pitfall may be avoided. We review the techniques for diagnosing synovial sarcoma and the importance of a high index of suspicion for endometriosis when investigating any soft-tissue mass in a female patient of reproductive age. Adequate pathological evaluation in conjunction with the correlating clinical and radiological information should help facilitate an accurate diagnosis.

 

 

 

Acta Obstet Gynecol Scand. 2017 Jun;96(6):751-760.

Endometriosis increases the risk of obstetrical and neonatal complications.

Berlac JF1Hartwell D2Skovlund CW2Langhoff-Roos J3Lidegaard Ø2.

 

Abstract

INTRODUCTION:

The objective of this study was to assess obstetrical complications and neonatal outcomes in women with endometriosis as compared with women without endometriosis.

MATERIAL AND METHODS:

National cohort including all delivering women and their newborns in Denmark 1997-2014. Data were extracted from the Danish Health Register and the Medical Birth Register. Logistic regression analysis provided odds ratios (OR) with 95% confidence intervals (CI). Sub-analyses were made for primiparous women with a singleton pregnancy and for women with endometriosis who underwent gynecological surgery before pregnancy.

RESULTS:

In 19 331 deliveries, women with endometriosis had a higher risk of severe preeclampsia (OR 1.7, 95% CI 1.5-2.0), hemorrhage in pregnancy (OR 2.3, 95% CI 2.0-2.5), placental abruption (OR 2.0, 95% CI 1.7-2.3), placenta previa (OR 3.9, 95% CI 3.5-4.3), premature rupture of membranes (OR 1.7, 95% CI 1.5-1.8), and retained placenta (OR 3.1, 95% CI 1.4-6.6). The neonates had increased risks of preterm birth before 28 weeks (OR 3.1, 95% CI 2.7-3.6), being small for gestational age (OR 1.5, 95% CI 1.4-1.6), being diagnosed with congenital malformations (OR 1.3, 95% CI 1.3-1.4), and neonatal death (OR 1.8, 95% CI 1.4-2.1). Results were similar in primiparous women with a singleton pregnancy. Gynecological surgery for endometriosis before pregnancy carried a further increased risk.

CONCLUSION:

Women with endometriosis had a significantly higher risk of several complications, such as preeclampsia and placental complications in pregnancy and at delivery. The newborns had increased risk of being delivered preterm, having congenital malformations, and having a higher neonatal death rate. Pregnant women with endometriosis require increased antenatal surveillance.

 

 

Adv Anat Pathol. 2017 Mar;24(2):88-98.

Perineural Pseudoinvasion: An Unusual Phenomenon in Nonmalignancies.

Moghimi M1Joukar FSalehi-Abargouei AMozayan MRAryanfar A.

 

Abstract

Perineural invasion (PNI) is characterized as tumoral or nontumoral cells invading in or around the nerves. The neural invasion is considered as a histopathologic characteristic for malignancy and is considered a mechanism for its spread. Both of these patterns usually portend a poor prognosis and very often are markers to prompt additional treatment. There are also some nonmalignancies representing PNI, including benign neoplasms, mimicking lesions, and disorders, such as chronic pancreatitis and endometriosis. The previously recommended terms are PNI, spread, or infiltration. To distinguish PNI in malignancies from that in nonmalignancies, we propose the term “perineural pseudoinvasion” to convey their nonmalignant behavior. Despite the low prevalence, awareness of this benign pseudoinvasion is necessary to avoid aggressive treatment and its misdiagnosis with malignancies. We conducted a systematic search in PubMed and Scopus databases up to December 2015 to find articles reporting PNI in nonmalignancies. After screening, 63 articles were identified as relevant. There were also 2 review articles discussing PNI in nonmalignancies. We aim to present an overview of the perineural pseudoinvasion and to discuss the previously published review articles.

 

 

J Cytol. 2017 Jan-Mar;34(1):61-63.

Endometriosis mimicking glandular atypia in a cervical cytology.

Rodriguez-Urrego PA1Dulcey-Hormiga IC2Barrera-Herrera LE2Suarez-Zamora DA2Palau-Lazaro MA1Buritica-Cifuentes C1.

 

Abstract

Endometriosis involving the uterine cervix is a rare condition that can lead to diagnostic errors in the interpretation of Pap smear. We report the case of a 41-year-old patient in whom the initial Pap smear revealed three-dimensional clusters of glandular cells with elongated nuclei, occasional mitosis, and atypia, which was interpreted as atypical glandular cells, not otherwise specified (NOS). The patient was taken to colposcopy and endocervical biopsy. Colposcopy was normal and the biopsy presented glands with elongated nuclei and surrounded by endometrial stroma admixed with normal endocervical glands. Immunohistochemical studies were reactive for CD10 in the stromal cells and vimentin in endometrioid glands. The findings were consistent with cervical endometriosis. Endometriosis in the cervix is an uncommon pathology that mimics malignancy and may be interpreted as atypical or glandular neoplasia in the cytology.

 

 

Reprod Sci. 2017 Oct;24(10):1346-1361

Molecular Characteristics of the Endometrium in Uterine Adenomyosis and Its Biochemical Microenvironment.

Yen CF1,2,3Huang SJ4,5Lee CL2,6Wang HS1,2,3Liao SK2,7.

 

Abstract

Adenomyosis, which manifests with focally or diffusely scattered endometrial tissue within the uterine myometrium, is an endometriosis-like disease with controversial pathogenesis and compromised reproductive outcomes. This review, including the in vitro and in vivo studies performed on human or mouse models, is aimed to summarize the specific molecular characteristics of endometrium in the biochemical microenvironments of uterine adenomyosis. Many studies attributed the endometrium as the main cause of pathogenesis, with evidence of differential genetic expression and/or epigenetic modulation as well as estrogen-induced epithelial-mesenchymal transition. However, some studies indicated that the myometrium could play a role in the development of disease, based on findings of smooth muscle metaplasia and/or fibroblast-to-myofibroblast transdifferentiation by the influence of local biochemical factors. To date, it remains unclear whether adenomyosis is a genetically determined or a microenvironmentally induced disorder or whether the dysregulation of local factors may elicit the alteration of genetic expression in the endometrium. Similarly, it is uncertain whether the endometrial characteristics would remain consistent or could change along with a woman’s reproductive life. Further longitudinal studies of the epigenetic controls or system biology are needed to elucidate the pathogenesis. Discovery of effective conservative treatments to improve the reproductive outcomes of patients with adenomyosis is still warranted.

 

 

J Clin Anesth. 2017 Feb;36:67-71.

Sonoanatomic indices of lumbar facet joints in patients with facetogenic back pain in comparison to healthy subjects.

Rahimzadeh P1Faiz HR2Baghaee AR3Nader ND4.

 

Abstract

BACKGROUND:

Nowadays, ultrasound is increasingly used with a great accuracy in performing nerve blocks for facet joint disease.

OBJECTIVES:

To measure sonoanatomic characteristics for the facet joints of lumbar vertebras in patients with facetogenic pain and healthy volunteers.

STUDY DESIGN:

Cross-sectional, observational study.

SETTING:

University-affiliated Specialty Clinic for Pain Management.

PATIENTS:

Twenty patients with facet joint disease (FJD) and 40 healthy volunteers (HVGs) were matched for age and sex, height, and weight. Patients with FJD were referred with complaints of pain in the left lumbar facet joints that twice responded favorably to ultrasound guided medial branch blocks.

INTERVENTION:

Medial branch blocks.

MEASUREMENT:

The interfacet joint distance (IFJD) between the third, the fourth, and the fifth lumbar vertebras and their depth from the level of skin (DFS) were measured bilaterally, using a high-resolution ultrasound in both groups.

RESULTS:

Thirty-one men and 29 women with average age of 41.5±9.5 years were enrolled. The IFJD for L3-L4 was 31.5±4.0 mm on the left side and 31.8±4.0 mm on the right side. The IFJD for L4-L5 was 31.3±4.4 mm on the left side and 31.5±4.0 mm on the right side. The IFJD was uniformly 2.2 mm shorter in the FJD group than those in the HVG group (P=.021). The measurements of DFS increased in lower vertebras (L3<L4<L5), bilaterally. With an exception of the left facet joints of L4 (P=.016), DFS measurements were similar in FJD and HVG groups.

LIMITATIONS:

The diagnosis of facet joint disease was merely clinical and the total number of the patients was relatively small.

CONCLUSION:

Interfacet distances of the lumbar vertebras are smaller in patients suffering from degenerative FJD compared with HVGs. Degenerative changes of intervertebral discs and partial reduction of space between 2 adjacent vertebras may contribute to this observation.

 

 

Hum Reprod. 2017 Apr 1;32(4):794-810.

Platelets impair natural killer cell reactivity and function in endometriosisthrough multiple mechanisms.

Du Y1Liu X1Guo SW1.

 

Abstract

STUDY QUESTION:

Do platelets have any role in the reduced cytotoxicity of natural killer (NK) cells in endometriosis?

SUMMARY ANSWER:

Platelets impair NK cell reactivity and function in endometriosis through multiple mechanisms.

WHAT IS KNOWN ALREADY:

Platelets play an important role in the development of endometriosis, and platelet-derived transforming growth factor-β1 (TGF-β1) suppresses the expression of NK Group 2, Member D (NKG2D) on NK cells, resulting in reduced cytotoxicity in women with endometriosis.

STUDY DESIGN SIZE, DURATION:

Experiments on mice with induced endometriosis in which either platelets, NK cells or both were depleted and controls (none depleted). In vitro experiments with NK cells, platelets and, as target cells, endometriotic epithelial cell and endometrial stromal cell lines.

PARTICIPANTS/MATERIALS SETTING METHODS:

Immunohistochemistry analysis of ectopic endometrial tissues from mice with induced endometriosis receiving either platelet depletion (PD), NK cell depletion, or both or none. Immunofluorescence, flow cytometry and gene expression analysis for major histocompatibility complex class I (MHC-I) expression in target cells. Cytotoxicity and degranulation assays and the measurement of interferon (IFN)-γ secretion for the evaluation of NK cytotoxicity. Flow cytometry and gene expression for the expression of NK cell receptors.

MAIN RESULTS AND THE ROLE OF CHANCE:

PD resulted in significantly reduced lesion weight in mice with induced endometriosis, but NK cell depletion as well as concomitant platelet and NK cell depletion increased the weight, suggesting that the anti-endometriosis effect of PD is mediated, at least in part, by increased NK cell cytotoxicity against endometriotic cells. Co-incubation of target cells with platelets resulted in rapid platelet coating as well as increased MHC-I expression in these cells, effectively providing a cloak of ‘pseudo-self’ to these cells to shield against NK cell lysis. It also reduced the expression of NKG2D ligands MICA and MICB and reduced the NK cell cytotoxicity. In addition, co-incubation of NK cells with platelets impaired the NK cell cytotoxicity as well. This impaired NK cell cytotoxicity was not due to the increased NK cell apoptosis, but, rather, through reduced NK cell degranulation and IFN-γ production, and reduced expression of activating receptors NKG2D and NKp46 and increased expression of inhibitory receptor KIR2DL1 in NK cells. Inhibition of TGF-β1 signaling partially restored the aberrant expression of NKG2D, NKp46 and KIR2DL1, and partially restored the impaired NK cell cytotoxicity induced by activated platelets and their releasate.

 

 

Acta Obstet Gynecol Scand. 2017 Jun;96(6):633-643.

An update on the diagnosis, surgical management, and fertility outcomes for women with endometrioma.

Cranney R1Condous G2,3Reid S4.

 

Abstract

Endometriosis is estimated to affect up to 50% of infertile women, and severity of endometriosis stage appears to correlate with reduced fertility. Ovarian endometriomas are found in up to 44% of women with endometriosis, and are significantly associated with the presence of pelvic deep infiltrating endometriosis, ovarian adhesions, and pouch of Douglas obliteration. Through the use of MEDLINE and PubMed databases, we conducted a literature review of all available research related to the diagnosis, surgical management and fertility outcomes for women with endometrioma. The evolving use of specialized transvaginal ultrasound for the diagnosis of endometrioma and related endometriotic pathologies can allow for preoperative mapping/staging of the disease, as well as appropriate surgical planning and fertility counseling. Surgical management of endometriomas appears to reduce markers of ovarian reserve, such as anti-Mullerian hormone, prompting concern of reduced fertility following surgery. Ovarian cystectomy appears to be superior to ablation in terms of endometrioma recurrence, pain symptoms and increased spontaneous conception rate among subfertile patients. Research is inconclusive as to which surgical method least damages ovarian reserve in the long term; however, bipolar hemostasis appears to be the most damaging technique and should be avoided. Surgical management should be individualized for women with endometrioma, and strong consideration should be given to the preoperative ovarian reserve status prior to performing ovarian cystectomy. Current evidence suggests that ovarian cystectomy does not improve reproductive outcomes for women with endometrioma undergoing assisted reproductive technology; however, the majority of studies have been performed retrospectively and more prospective studies are needed.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Apr;211:48-55.

Potentized estrogen in homeopathic treatment of endometriosis-associated pelvic pain: A 24-week, randomized, double-blind, placebo-controlled study.

Teixeira MZ1Podgaec S2Baracat EC3.

 

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of potentized estrogen compared to placebo in homeopathic treatment of endometriosis-associated pelvic pain (EAPP).

STUDY DESIGN:

The present was a 24-week, randomized, double-blind, placebo-controlled trial that included 50 women aged 18-45 years old with diagnosis of deeply infiltrating endometriosis based on magnetic resonance imaging or transvaginal ultrasound after bowel preparation, and score≥5 on a visual analogue scale (VAS: range 0 to 10) for endometriosis-associated pelvic pain. Potentized estrogen (12cH, 18cH and 24cH) or placebo was administered twice daily per oral route. The primary outcome measure was change in the severity of EAPP global and partial scores (VAS) from baseline to week 24, determined as the difference in the mean score of five modalities of chronic pelvic pain (dysmenorrhea, deep dyspareunia, non-cyclic pelvic pain, cyclic bowel pain and/or cyclic urinary pain). The secondary outcome measures were mean score difference for quality of life assessed with SF-36 Health Survey Questionnaire, depression symptoms on Beck Depression Inventory (BDI), and anxiety symptoms on Beck Anxiety Inventory (BAI).

RESULTS:

The EAPP global score (VAS: range 0 to 50) decreased by 12.82 (P<0.001) in the group treated with potentized estrogen from baseline to week 24. Group that used potentized estrogen also exhibited partial score (VAS: range 0 to 10) reduction in three EAPP modalities: dysmenorrhea (3.28; P<0.001), non-cyclic pelvic pain (2.71; P=0.009), and cyclic bowel pain (3.40; P<0.001). Placebo group did not show any significant changes in EAPP global or partial scores. In addition, the potentized estrogen group showed significant improvement in three of eight SF-36 domains (bodily pain, vitality and mental health) and depression symptoms (BDI). Placebo group showed no significant improvement in this regard. These results demonstrate superiority of potentized estrogen over placebo. Few adverse events were associated with potentized estrogen.

CONCLUSIONS:

Potentized estrogen (12cH, 18cH and 24cH) at a dose of 3 drops twice daily for 24 weeks was significantly more effective than placebo for reducing endometriosis-associated pelvic pain.

 

 

J Ovarian Res. 2017 Feb 10;10(1):9

Characterization of ovarian clear cell carcinoma using target drug-based molecular biomarkers: implications for personalized cancer therapy.

Li M1,2Li H1,2Liu F1Bi R3Tu X3Chen L1,2Ye S1Cheng X4.

 

Abstract

BACKGROUND:

It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC).

METHODS:

Seven candidate drug-based molecular biomarkers, human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), breast cancer susceptibility gene 2 (BRCA2) and programmed death-ligand 1 (PD-L1) were measured in 96 ovarian CCC and 113 HGSC by immunohistochemistry in paraffin embedded tissues. The relationship between these biomarkers and clinicopathological factors were explored.

RESULTS:

The expression level of four of the seven drug-based molecular biomarkers was markedly different between HGSC and CCC. High expression levels of HER2 and PD-L1 were more commonly observed in CCC patients (12.6% vs 2.7%, 21.1% vs 11.6%, P = 0.006, 0.064, respectively), while loss of BRCA1 and BRCA2 expression were more frequently occurred in HGSC patients (72.6% vs 54.3%, 89.4% vs 79.8%, P = 0.007, 0.054, respectively). Survival analysis showed that five of seven biomarkers had prognostic values but varied between subtypes. Furthermore, EGFR expressed frequently in CCC patients with endometriosis than in HGSC patients (44.4% vs 8.3%, P = 0.049). AURKA and PD-L1 correlated with the resistance to platinum-based chemotherapy in CCC patients (P = 0.043, 0.028, respectively) while no similar results were observed in HGSC patients.

CONCLUSION:

Ovarian CCC showed a markedly different expression map of drug-based molecular biomarkers from HGSC, which suggested a new personalized target therapy in this rare subtype.

 

 

Fertil Steril. 2017 Mar;107(3):549-554

Surgery for endometriosis: beyond medical therapies.

Singh SS1Suen MW2.

 

Abstract

Endometriosis-associated pelvic pain and subfertility may be managed medically in many cases; however, the surgical management of this insidious disease remains a necessary part of the treatment algorithm. Laparoscopy for diagnosis alone is rarely indicated with the advancements in preoperative imaging. When surgery is performed, the ideal goal would be a therapeutic and effective surgical intervention based on the preoperative evaluation. Surgery for women with pain due to endometriosis may be indicated in patients who cannot or do not wish to take medical therapies; acute surgical or pain events; deep endometriosis; during concomitant management of other gynecologic disorders; and patients seeking fertility with pain. The role of surgery for endometriosis-related subfertility may be considered in those with hydrosalpinges undergoing IVF; management of ovarian endometriomas in specific circumstances; and when a patient requests surgery as an alternative to assisted reproductive technology (ART). Surgery for ovarian endometriomas requires special attention due to the risk of potential harm on future fertility. Finally, a combined approach of surgery followed by postoperative medical therapy offers the best long-term outcomes for recurrence of disease and symptoms. A patient-centered approach and a goal-oriented approach are essential when determining the options for care in this population.

 

 

Fertil Steril. 2017 Mar;107(3):523-532.

Biomarkers in endometriosis: challenges and opportunities.

Ahn SH1Singh V2Tayade C3.

 

Abstract

Endometriosis is a debilitating gynecologic disease affecting millions of women across the world, with symptoms including dysmenorrhea, chronic pelvic pain, and infertility. Theorized to stem from the phenomenon of retrograde menstruation, the diagnosis of endometriosis is typically delayed by 8-10 years owing to misinterpretation of symptoms as common menstrual cramps in adolescent girls and young women. With increased incidence of endometriosis in young girls correlated with earlier menarche, the development of diagnostic biomarkers is imperative for diagnosing and treating women afflicted with endometriosis as early as we can. In the past few years, multiple reviews highlighted the list of potential diagnostic candidates in peritoneal fluid, blood, urine, and endometrial biopsies from endometriosis patients in different stages of disease and menstrual cycle. In this review, we explore the opportunities and challenges facing the field of diagnostic biomarkers for endometriosis. We highlight the importance of eutopic endometrium as a source of potential diagnostic biomarkers by looking at the expression levels of noncoding RNA in tissue as well as in blood. Finally, we discuss some of the challenges that hinder our efforts in validating candidate diagnostic biomarkers for endometriosis.

 

 

J Pediatr Adolesc Gynecol. 2017 Oct;30(5):560-567.

Dienogest 2 mg Daily in the Treatment of Adolescents with Clinically Suspected Endometriosis: The VISanne Study to Assess Safety in ADOlescents.

Ebert AD1Dong L2Merz M2Kirsch B2Francuski M2Böttcher B3Roman H4Suvitie P5Hlavackova O6Gude K2Seitz C2.

 

Abstract

STUDY OBJECTIVE:

To study the safety and efficacy of dienogest 2 mg in adolescents with suspected endometriosis.

DESIGN:

A 52-week, open-label, single-arm study.

SETTING:

In 21 study centers, in 6 European countries.

PARTICIPANTS:

Adolescents aged 12 to younger than 18 years with clinically suspected or laparoscopically confirmed endometriosis.

INTERVENTIONS:

Dienogest 2 mg once daily.

MAIN OUTCOME MEASURES:

The primary end point was relative change in lumbar spine (L2-L4) bone mineral density (BMD) measured using dual-energy x-ray absorptiometry. A key secondary end point was change in endometriosis-associated pain assessed using a visual analogue scale.

RESULTS:

Of 120 patients screened, 111 comprised the full-analysis set (ie, patients who took ≥1 dose of study drug and had ≥1 post-treatment observation) and 97 (87.4%) completed the study. Mean lumbar BMD at baseline was 1.1046 (SD, 0.1550) g/cm2. At the end of dienogest treatment (EOT; defined as at 52 weeks or premature study discontinuation), mean relative change in BMD from baseline was -1.2% (SD, 2.3%; n = 103). Follow-up measurement 6 months after EOT in the subgroup with decreased BMD at EOT (n = 60) showed partial recovery in lumbar BMD (mean change from baseline: -2.3% at EOT, -0.6% 6 months after EOT). Mean endometriosis-associated pain score was 64.3 (SD, 19.1) mm at baseline and decreased to 9.0 (SD, 13.9) mm by week 48.

CONCLUSION:

In adolescents with suspected endometriosis, dienogest 2 mg for 52 weeks was associated with a decrease in lumbar BMD, followed by partial recovery after treatment discontinuation. Endometriosis-associated pain was substantially reduced during treatment. Because bone accretion is critical during adolescence, results of the VISanne study to assess safety in ADOlescents (VISADO) study highlights the need for tailored treatment in this population, taking into account the expected efficacy on endometriosis-associated pain and an individual’s risk factors for osteoporosis.

 

 

Geburtshilfe Frauenheilkd. 2017 Jan;77(1):66-72.

Everolimus as an mTOR Inhibitor Suppresses Endometriotic Implants: an Experimental Rat Study.

Kacan T1Yildiz C2Baloglu Kacan S3Seker M1Ozer H4Cetin A2.

 

Abstract

Introduction Mammalian target of rapamycin is a pathway to block apoptosis. Recent studies showed that the activity of mammalian target of rapamycin pathway increases in endometriotic lesions. Aim of the present study was to study the effect of everolimus agent, a rapamycin analog, in an experimental endometriosis model. Materials and Methods Endometriosis established by the autotransplantation of uterine tissue in the peritoneal cavity was confirmed in 24 rats. The animals were then randomly divided into three groups to receive either everolimus (1.5 mg/kg/day, p. o.), anastrozole (0.004 mg/day, p. o.), or normal saline (0.1 mL, i. p.) for 14 days. Endometriotic foci were excised, stained with hematoxylin and eosin, and endometriosis was scored semiquantitatively. In addition, immunohistochemical examination were performed using primary antibodies of vascular endothelial growth factor, CD117, and Bax. Results Both anastrozole and everolimus lowered endometriosis scores. Significant decreases in ovarian follicles were observed following anastrozole treatment but not everolimus treatment. Conclusion Through its apoptosis-promoting effect, everolimus suppressed endometriotic foci without negatively affecting ovarian reserve. These findings support the hypothesis that everolimus merits further study on the way to developing a new endometriosis drug.

 

 

Wideochir Inne Tech Maloinwazyjne. 2016;11(4):253-258.

Post-laparoscopy predictive factors of achieving pregnancy in patients treated for infertility.

Wdowiak A1Wdowiak E2Stec M3Bojar I4.

 

Abstract

INTRODUCTION:

Laparoscopy is a long-established diagnostic and therapeutic method for treating women suffering from infertility. The application of this method of treatment can help achieve pregnancy only if there is correct classification of patients and evaluation of their partner’s reproductive capacity. The main predictors of achieving pregnancy in a couple treated for infertility are the woman’s age, her ovarian reserve, tubal patency, the presence of endometriosis and quality of sperm parameters.

AIM:

To evaluate the effect of endometriosis, ovarian reserve and selected parameters of semen on the effect of achieving pregnancy in patients undergoing laparoscopy.

MATERIAL AND METHODS:

The most significant predictor of pregnancy in patients undergoing laparoscopy due to infertility was found to be anti-Mullerian hormone (AMH) level after laparoscopy, and the main parameters of semen partners were density, motility and morphology. The number of achieved pregnancies after the laparoscopic treatment of infertility was lower in patients diagnosed with endometriosis, and depended on the severity of the condition.

RESULTS:

As a result of laparoscopic treatment of endometriosis, we found a decrease in ovarian reserve measured by means of AMH.

CONCLUSIONS:

The most important predictors of pregnancy in patients who underwent laparoscopy due to infertility are post-laparoscopy AMH levels and the main parameters of the partner’s semen: density, motility and morphology. The number of pregnancies after laparoscopic treatment is lower in patients diagnosed with endometriosis, and depends on the severity of the conditio.

 

 

Cancer Causes Control. 2017 May;28(5):447-457

Synchronous endometrial and ovarian carcinomas: predictors of risk and associations with survival and tumor expression profiles.

Kelemen LE1,2Rambau PF3,4Koziak JM5Steed H6Köbel M4.

 

Abstract

PURPOSE:

Synchronous endometrial and ovarian tumors (SEOs) are diagnosed in 10% of ovarian cancer patients. We examined predictors of SEOs, evaluated associations of SEOs with survival and characterized ovarian tumor profiles using immunohistochemistry.

METHODS:

We included patients with endometrioid (n = 180) and clear cell (n = 165) ovarian carcinoma identified from the Alberta Cancer Registry between 1979 and 2010 for whom we abstracted medical records and constructed tumor tissue microarrays (TMAs). A concurrent diagnosis of endometrial cancer was obtained from the medical chart. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs. Protein expression in ovarian tumors of patients with and without SEOs was evaluated using Fisher’s exact test.

RESULTS:

Comparing 52 patients with SEO tumors to 293 patients with endometrioid or clear cell ovarian carcinomas, endometriosis at the ovary (OR = 0.45, 95% CI = 0.23-0.87, p = 0.02) was the strongest predictor of decreased risk in multivariable models. Premenopausal status (OR = 2.17, 95% CI = 0.92-5.13, p = 0.08) and lower pre-treatment CA125 levels (OR = 0.17, 95% CI = 0.02-1.32, p = 0.09) showed weaker associations. There were no significant differences in survival between patients with or without SEO tumors. More patients with SEO tumors compared to endometrioid ovarian carcinoma were deficient in MLH1, PMS2 and PTEN (p ≤ 0.03).

CONCLUSIONS:

Endometriosis may not be the mechanism by which SEO cancers arise. Altered tumor oncoprotein expression between women with and without SEOs indicates important biological differences although this did not translate into prognostic differences.

 

 

J Robot Surg. 2017 Jun;11(2):97-109.

Robotic-assisted laparoscopy in reproductive surgery: a contemporary review.

Jayakumaran J1Patel SD2Gangrade BK2Narasimhulu DM3Pandian SR4Silva C2.

 

Abstract

Robotic surgery is a conceptual fusion of the conventional open surgery and the minimally invasive laparoscopic surgery. We reviewed the current role of robotic-assisted laparoscopy in the field of reproductive surgery by a literature search in PubMed database. We analyzed the reported advantages and limitations of the use of robotics in reproductive surgeries like myomectomy, tubal reanastomosis, endometriosis, ovarian tissue cryopreservation, and ovarian transposition. Overall, robotic assistance in reproductive surgery resulted in decreased blood loss, less post-operative pain, shorter hospital stay, and faster convalescence, whereas reproductive outcomes were similar to open/laparoscopic approaches. The main drawbacks of robotic surgery were higher cost and longer operating times. It is as safe and effective as the conventional laparoscopy and represents a reasonable alternate to abdominal approach. Procedures that are technically challenging with the conventional laparoscopy can be performed with robotic assistance. It has advantages of improved visualization and Endowrist™ movements allowing precise suturing. This helps to overcome the limitations of laparoscopy, especially in complicated procedures, and may shorten the steep learning curve in minimal invasive surgery. Randomized controlled trials looking at both short- and long-term outcomes are warranted to strengthen the role of robotic surgery in the field of reproductive surgery.

 

 

Pathologica. 2016 Sep;108(3):144-147.

A puzzling ovarian tumour: pregnancy luteoma with diffuse endometriosis.

Limaiem F1Bouraoui S1Bouslama S1Lahmar A1Mzabi S1.

 

Abstract

BACKGROUND:

Pregnancy luteoma is a distinctive non-neoplastic hormone dependent lesion arising in pregnancy and mimicking an ovarian tumour. Fewer than 200 cases have been described in the English-language literature. Its clinical and morphological features are characteristic and must be considered in order to prevent diagnostic misinterpretation. To the best of our knowledge the association of pregnancy luteoma with endometriosis has not been reported in literature to date.

CASE REPORT:

A 30-year-old pregnant woman with no particular past medical history, consulted her gynaecologist at 17 weeks gestation for routine check-up. The patient was asymptomatic and did not show any signs of virilization. Ultrasonography disclosed a left adnexal heterogeneous mass measuring 7 cm in diameter with intramural vegetations. The right ovary was unremarkable. The patient underwent salpingo-oophorectomy considering the imaging findings were suspicious for malignancy. Histologically, the lesion was constituted of large sheets of luteinized polygonal cells with abundant eosinophilic cytoplasm and small round nuclei devoid of atypia and mitotic figures. In addition, there were several ectopic endometrial glands surrounded by abundant decidualized or edematous stroma. Immunohistochemically, these glands were immunoreactive for cytokeratin 7. The final pathological diagnosis was pregnancy luteoma associated with diffuse endometriosis.

CONCLUSIONS:

Because of its relative rarity, pregnancy luteoma is likely to be clinically misinterpreted and overtreated, as in the present case.

 

 

Acta Reumatol Port. 2017 Jan-Mar;42(1):26-31.

Carbonic anhydrase I and II autoantibodies in Behçet’s disease.

Mentese A1Alver A1Demir S2Sumer A3Ozer Yaman S1Karkucak M1Aydin Capkin A4Us Altay D5Turan I6.

 

Abstract

BACKGROUND:

Behçet’s disease is a vasculitis, seen more frequently around the Mediterranean and the Far East, and evinces with oral and genital ulcerations, skin lesions and uveitis. Carbonic anhydrase (CA) is a metalloenzyme which is widely distributed in the living world, and it is essential for the regulation of acid-base balance. Anti-CA antibodies have been reported in many disorders, such as systemic lupus erythematosus, Sjögren’s syndrome, rheumatoid arthritis, endometriosis, idiopathic chronic pancreatitis, type 1 diabetes and Graves’ disease. The goal of this study was to investigate CA I and II autoantibodies in Behçet’s disease (BD).

METHODS:

35 patients with BD and 29 healthy controls were included in the study and CA I and II autoantibody levels were investigated by ELISA.

RESULTS:

The CA I and II autoantibody levels of BD group were significantly higher than the healthy group (p=0.013, p inf 0.0001, respectively). A cut-off value of 0.250 ABSU for anti-CA I was associated with 34 % sensitivity and 100 % specificity and a cut-off value of 0.171 ABSU for anti-CA II was associated with 54 % sensitivity and 100 % specificity for predicting BD.

CONCLUSION:

The CA I and II autoantibody levels in patients with BD were found higher compared to control group and the results suggest that CA I and II autoantibodies may be involved in the pathogenesis of BD.

 

 

Intern Med. 2017;56(4):409-412.

Venous Thromboembolism Due to Oral Contraceptive Intake and Spending Nights in a Vehicle -A Case from the 2016 Kumamoto Earthquakes.

Sueta D1Akahoshi ROkamura YKojima SIkemoto TYamamoto EIzumiya YTsujita KKaikita KKatabuchi HHokimoto S.

 

Abstract

A 40-year-old woman experiencing sudden dyspnea went to her personal doctor for advice. She was previously diagnosed with endometriosis and prescribed oral contraceptives for treatment. During earthquakes, she spent 7 nights sleeping in a vehicle. The patient had swelling and pain in her left leg and high D-dimer concentration levels. A contrast-enhanced computed tomography scan revealed a contrast deficit in the bilateral pulmonary artery and in the left lower extremity. She was diagnosed with pulmonary thromboembolism (PTE), and anticoagulation therapy was initiated. This present case is the first report of PTE attributed to the use of oral contraceptives after earthquakes.

 

 

Biol Reprod. 2017 Feb 1;96(2):302-312.

A novel homologous model for noninvasive monitoring of endometriosisprogression.

Ferrero H1,2Buigues A2,3Martínez J2Simón C1,2,3Pellicer A1,2,4,3Gómez R2.

 

Abstract

To date, several groups have generated homologous models of endometriosis through the implantation of endometrial tissue fluorescently labeled by green fluorescent protein (GFP) or tissue from luciferase-expressing transgenic mice into recipient animals, enabling noninvasive monitoring of lesion signal. These models present an advantage over endpoint models, but some limitations persist; use of transgenic mice is laborious and expensive, and GFP presents poor tissue penetration due to the relatively short emission wavelength. For this reason, a homologous mouse model of endometriosis that allows in vivo monitoring of generated lesions over time and mimics human lesions in recipient mice would be most desirable. In this regard, using C57BL/6 and B6N-Tyrc-Brd/BrdCrCrl mice, we optimized a decidualization protocol to obtain large volumes of decidual endometrium and mimic human lesions. Subsequently, to obtain a more robust and reliable noninvasive monitoring of lesions, we used the fluorescent reporter mCherry, which presents deeper tissue penetration and higher photostability, showing that endometrial tissue was properly labeled with 1 × 108 PFU/mL mCherry adenoviral vectors. mCherry-labeled endometriotic tissue was implanted in recipient mice, generating lesions that displayed characteristics typical of human endometriotic lesions, such as epithelial cells forming glands, local inflammation, collagen deposits, and new vessel formation. In vivo monitoring demonstrated that subcutaneous implantation on ventral abdomen of recipient mice provided the most intense and reliable signal for noninvasive lesion monitoring over a period of at least 20 days. This homologous model improves upon previously reported models of endometriosis and provides opportunities to study mechanism underlying endometriotic lesion growth and progression. We created a cost-effective but accurate homologous mouse model of endometriosis that allows the study of growth and progression of endometriotic lesions over early time points in lesion development through noninvasive monitoring.

 

 

Hum Reprod. 2017 May 1;32(5):999-1008.

Cost-effectiveness of ‘immediate IVF’ versus ‘delayed IVF’: a prospective study.

Eijkemans MJC1,2Kersten FAM3Lintsen AME3Hunault CC2,4Bouwmans CAM5Roijen LH5Habbema JDF2Braat DDM3.

 

Abstract

STUDY QUESTION:

How does the cost-effectiveness (CE) of immediate IVF compared with postponing IVF for 1 year, depend on prognostic characteristics of the couple?

SUMMARY ANSWER:

The CE ratio, i.e. the incremental costs of immediate versus delayed IVF per extra live birth, is the highest (range of €15 000 to >€60 000) for couples with unexplained infertility and for them depends strongly on female age and the duration of infertility, whilst being lowest for endometriosis (range 8000-23 000) and, for such patients, only slightly dependent on female age and duration of infertility.

WHAT IS KNOWN ALREADY:

A few countries have guidelines for indications of IVF, using the diagnostic category, female age and duration of infertility. The CE of these guidelines is unknown and the evidence base exists only for bilateral tubal occlusion, not for the other diagnostic categories.

STUDY DESIGN, SIZE, DURATION:

A modelling approach was applied, based on the literature and data from a prospective cohort study among couples eligible for IVF or ICSI treatment, registered in a national waiting list in The Netherlands between January 2002 and December 2003.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

A total of 5962 couples was included. Chances of natural ongoing pregnancy were estimated from the waiting list observations and chances of ongoing pregnancy after IVF from follow-up data of couples with primary infertility that began treatment. Prognostic characteristics considered were female age, duration of infertility and diagnostic category. Costs of IVF were assessed from a societal perspective and determined on a representative sample of patients. A cost-effectiveness comparison was made between two scenarios: (I) wait one more year and then undergo IVF for 1 year and (II) immediate IVF during 1 year, and try to conceive naturally in the following year. Comparisons were made for strata determined by the prognostic factors. The final outcome was a live birth.

MAIN RESULTS AND THE ROLE OF CHANCE:

The gain in live birth rate of the immediate IVF scenario versus postponed IVF increased with female age, and was independent from diagnostic category or duration of infertility. By contrast, the corresponding increase in costs primarily depended on diagnostic category and duration of infertility. The lowest CE ratio was just below €10 000 per live birth for endometriosis from age 34 onwards at 1 year duration. The highest CE ratio reached €56 000 per live birth for unexplained infertility at age 30 and 3 years duration, dropping to values below € 30 000 per live birth from age 32 onwards. It reached values below €20 000 per live birth with 3 years duration at age 34 and older. The CE ratio was in between for the three other diagnostic categories (i.e. Male infertility, Hormonal and Immunological/Cervical).

LIMITATIONS, REASONS FOR CAUTION:

We applied estimates of chances with IVF, excluding frozen embryos, for which we had no data. Therefore, we do not know the effect of frozen embryo transfers on the CE.

WIDER IMPLICATIONS OF THE FINDINGS:

The duration of infertility at which IVF becomes cost-effective depends, firstly, on the level of society’s willingness to pay for one extra live birth, and secondly, given a certain level of willingness to pay, on the woman’s age and the diagnostic category. In current guidelines, the chances of a natural conception should always be taken into account before deciding whether to start IVF treatment and at which time.

STUDY FUNDING/COMPETING INTEREST(S):

Supported by Netherlands Organisation for Health Research and Development (ZonMW, grant 945-12-013). ZonMW had no role in designing the study, data collection, analysis and interpretation of data or writing of the report. Competing interests: none.

 

Reprod Sci. 2017 Nov;24(11):1503-1511.

Effects of an Antagonistic Analog of Growth Hormone-Releasing Hormone on Endometriosis in a Mouse Model and In Vitro.

Köster F1Jin L2Shen Y3Schally AV4,5,6Cai RZ4,5,6Block NL4,5,6Hornung D7Marschner G1Rody A1Engel JB8Finas D9.

 

Abstract

Endometriosis is a benign gynecologic disorder causing dysmenorrhea, pelvic pain, and subfertility. Receptors for the growth hormone-releasing hormone (GHRH) were found in endometriotic tissues. Antagonists of GHRH have been used to inhibit the growth of endometriotic endometrial stromal cells. In this study, the GHRH receptor splice variant (SV) 1 was detected in human endometrial tissue samples by Western blots and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The highest messenger RNA (mRNA) and protein levels of SV1 were found in eutopic endometrium from patients with endometriosis compared to ectopic endometriotic tissues and endometrium from normal patients. The highest expression for GHRH mRNA was found by qRT-PCR in ectopic endometriosis lesions. In an in vivo mouse model with human endometrial explants from patients with endometriosis, 10 μg MIA-602 per day resulted in significantly smaller human endometrial xenotransplants after 4 weeks compared to mice treated with vehicle. The endometrial tissues expressed SV1 before and after xenotransplantation. The proliferation of endometrial stromal cells as well as the endometriosis cell lines 12-Z and 49-Z was decreased by exposure to 1 μM MIA-602 after 72 hours. The protein levels of epithelial growth factor receptors in 12-Z and 49-Z cell lines were reduced 48 and 72 hours after the administration of 1 μM MIA-602. MIA-602 decreased the activation of the MAP-kinases ERK-1/2. Our study demonstrates the presence of SV1 receptor as a target for treatment with GHRH antagonist in endometriosis. Endometrial tissues respond to MIA-602 with inhibition of proliferation in vitro and in vivo. The use of MIA-602 could be an effective supplement to the treatment strategies in endometriosis.

 

 

Am J Obstet Gynecol. 2017 Jun;216(6):582.

Postoperative maintenance levonorgestrel-releasing intrauterine system and endometrioma recurrence: a randomized controlled study.

Chen YJ1Hsu TF2Huang BS3Tsai HW4Chang YH5Wang PH6.

 

Abstract

BACKGROUND:

According to 3 randomized trials, the levonorgestrel-releasing intrauterine system significantly reduced recurrent endometriosis-related pelvic pain at postoperative year 1. Only a few studies have evaluated the long-term effectiveness of the device for preventing endometrioma recurrence, and the effects of a levonorgestrel-releasing intrauterine system as a maintenance therapy remain unclear.

OBJECTIVE:

The objective of the study was to evaluate whether a maintenance levonorgestrel-releasing intrauterine system is effective for preventing postoperative endometrioma recurrence.

STUDY DESIGN:

From May 2011 through March 2012, a randomized controlled trial including 80 patients with endometriomas undergoing laparoscopic cystectomy followed by six cycles of gonadotropin-releasing hormone agonist treatment was conducted. After surgery, the patients were randomized to groups that did or did not receive a levonorgestrel-releasing intrauterine system (intervention group, n = 40, vs control group, n = 40). The primary outcome was endometrioma recurrence 30 months after surgery. The secondary outcomes included dysmenorrhea, CA125 levels, noncyclic pelvic pain, and side effects.

RESULTS:

Endometrioma recurrence at 30 months did not significantly differ between the 2 groups (the intervention group, 10 of 40, 25% vs the control group 15 of 40, 37.5%; hazard ratio, 0.60, 95% confidence interval, 0.27-1.33, P = .209). The intervention group exhibited a lower dysmenorrhea recurrence rate, with an estimated hazard ratio of 0.32 (95% confidence interval, 0.12-0.83, P = .019). Over a 30 month follow-up, the intervention group exhibited a greater reduction in dysmenorrhea as assessed with a visual analog scale score (mean ± SD, 60.8 ± 25.5 vs 38.7 ± 25.9, P < .001, 95% confidence interval, 10.7-33.5), noncyclic pelvic pain visual analog scale score (39.1 ± 10.9 vs 30.1 ± 14.7, P = .014, 95% confidence interval, 1.9-16.1), and CA125 (median [interquartile range], -32.1 [-59.1 to 14.9], vs -15.6 [-33.0 to 5.0], P = .001) compared with the control group. The number-needed-to-treat benefit for dysmenorrhea recurrence at 30 months was 5. The number of recurrent cases requiring further surgical or hormone treatment in the intervention group (1 of 40, 2.5%, 95% confidence interval, -2.3% to 7.3%) was significantly lower than that in the control group (8 of 40, 20%, 95% confidence interval, 7.6-32.4%; P = .031).

CONCLUSION:

Long-term maintenance therapy using a levonorgestrel-releasing intrauterine system is not effective for preventing endometrioma recurrence.

 

 

Case Rep Obstet Gynecol. 2017;2017:7239018.

Cystic Endometrioma with Coexisting Fibroma Originating in a Supernumerary Ovary in the Rectovaginal Pouch.

Ogishima D1Sakaguchi A2Kodama H2Ogura K2Miwa A1Sugimori Y1Matuoka S1Matsumoto T2.

 

Abstract

A supernumerary ovary is an exceedingly rare disorder, in which the structure containing ovarian tissue is located at some distance from the normally placed ovary. 16 cases of endometriosis or tumors originating in a supernumerary ovary have been published in the English literature, but no case of coexisting endometriosis and a tumor has been published. We present the case of a 40-year-old female with cystic endometrioma with coexisting fibroma originating in a supernumerary ovary in the rectovaginal pouch. The present case is the first to be reported with coexisting endometriosis and a tumor originating in a supernumerary ovary. Our experience with this case and the results of our previous studies of rectovaginal endometriosis indicated that the possibility of originating in a supernumerary ovary shall be examined in cases of cystic endometrioma in the rectovaginal pouch.

 

 

Med J Islam Repub Iran. 2016 Oct 24;30:433

Ultrasound-guided fascia iliaca compartment block in orthopedic fractures: Bupivacaine 0.2% or 0.3%?

Rahimzadeh P1Imani F2Sayarifard A3Sayarifard S4Faiz SH5.

 

Abstract

Background: Postoperative pain is one of the major problems in patients with femoral or hip fracture. Current study investigates the effect of 0.2% and 0.3% bupivacaine in ultrasound-guided fascia iliaca compartment block (FICB) on postoperative pain. Methods: This randomized clinical trial study was conducted in Rasoul Akram Hospital of Iran University of Medical Sciences. Forty-eight patients with femoral or hip fractures who were candidates for surgery underwent FICB, divided into two groups receiving bupivacaine in 0.2% and 0.3% concentrations. Pain was evaluated with Visual Analog Scale (VAS) at times 2, 6, 12, 24, and 48 hours after surgery. Need for opioids, nausea and vomiting after surgery, patients’ satisfaction with pain control and motor block were also recorded. T-test or Mann- Whitney U test and Repeated measure ANOVA was used for analysis. Results: Pain score after surgery was significantly lower in groups receiving 0.3% than the group receiving 0.2% concentration. Patients’ satisfaction with pain control in 0.2% group was significantly higher (p=0.04). Time to analgesic onset in both groups had no significant differences (p=0.5). The incidence of nausea and vomiting (p=0.5) and opioid consumption (p=0.1) between the two groups showed no significant difference. Conclusion:In femoral or hip fracture, bupivacaine with 0.3% concentration in fascia iliaca compartment block can cause lower pain score compared to bupivacaine with 0.2% concentration, but patients’ satisfaction with pain control and severity of motor block is higher in bupivacaine 0.2%.

 

 

Semin Reprod Med. 2017 Mar;35(2):173-180.

MicroRNAs and Endometriosis: Distinguishing Drivers from Passengers in Disease Pathogenesis.

Nothnick WB1.

 

Abstract

Endometriosis is a disease common in women of reproductive age, characterized by pelvic pain and infertility. Despite its prevalence, the factors and mechanisms which contribute to the development and survival of ectopic lesions remain uncertain. MicroRNAs (miRNAs) are small RNA molecules that regulate posttranscriptional gene regulation which have been proposed to contribute to the pathogenesis of many diseases including that of endometriosis. This review summarizes the results of initial studies describing differentially expressed miRNAs between endometriotic lesion tissue and eutopic endometrium. Focus then moves toward discussion of studies on examining function of differentially expressed miRNAs to determine if they play a permissive role (driver of the disease) in events conducive to endometriosis progression/survival. Included in this discussion are the potential targets of these miRNAs and how their mis-expression may contribute to the disease. Limitations and challenges faced in studying miRNAs and endometriosis pathogenesis and recommendations to overcome these hurdles are presented at the end.

 

 

Gynecol Oncol. 2017 Apr;145(1):142-147.

Genetic risk factors for ovarian cancer and their role for endometriosis risk.

Burghaus S1Fasching PA2Häberle L3Rübner M1Büchner K1Blum S1Engel A3Ekici AB4Hartmann A5Hein A1Beckmann MW1Renner SP1.

 

Abstract

OBJECTIVE:

Several genetic variants have been validated as risk factors for ovarian cancer. Endometriosis has also been described as a risk factor for ovarian cancer. Identifying genetic risk factors that are common to the two diseases might help improve our understanding of the molecular pathogenesis potentially linking the two conditions.

METHODS:

In a hospital-based case-control analysis, 12 single nucleotide polymorphisms (SNPs), validated by the Ovarian Cancer Association Consortium (OCAC) and the Collaborative Oncological Gene-environment Study (COGS) project, were genotyped using TaqMan® OpenArray™ analysis. The cases consisted of patients with endometriosis, and the controls were healthy individuals without endometriosis. A total of 385 cases and 484 controls were analyzed. Odds ratios and P values were obtained using simple logistic regression models, as well as from multiple logistic regression models with adjustment for clinical predictors.

RESULTS:

rs11651755 in HNF1B was found to be associated with endometriosis in this case-control study. The OR was 0.66 (95% CI, 0.51 to 0.84) and the P value after correction for multiple testing was 0.01. None of the other genotypes was associated with a risk for endometriosis.

CONCLUSIONS:

As rs11651755 in HNF1B modified both the ovarian cancer risk and also the risk for endometriosis, HNF1B may be causally involved in the pathogenetic pathway leading from endometriosis to ovarian cancer.

 

 

J Minim Invasive Gynecol. 2017 May – Jun;24(4):653-658.

Endometriosis in Hydatid Cysts of Morgagni: A Retrospective Cohort Study of Another Atypical Manifestation of Endometriosis.

Gupta S1Gavard JA2Kraus E2Yeung P Jr2.

 

Abstract

STUDY OBJECTIVE: To report on the presence and rate of endometriosis in hydatid cysts of Morgagni found at the time of excision surgery for endometriosis and to describe any association of endometriosis in hydatid cysts of Morgagni with preoperative or operative factors.

DESIGN:

A retrospective cohort study (Canadian Task Force Classification II-2).

SETTING:

The Center for Endometriosis at Saint Louis University, a tertiary referral center for endometriosis.

PATIENTS:

Women who underwent optimal excision surgery for suspected endometriosis because of chronic pelvic pain and/or infertility and who also had hydatid cysts of Morgagni removed at the time of surgery when found.

INTERVENTIONS:

Preoperative and operative data were collected prospectively.

MAIN OUTCOME MEASURES:

The rate of endometriosis in hydatid cysts of Morgagni. Secondary measures included are the rate of hydatid cysts of Morgagni in patients with pelvic pain or infertility with and without endometriosis in the cysts.

RESULTS:

The overall prevalence of endometriosis in hydatid cysts of Morgagni was 11.3%. Patients with pelvic pain had a higher rate (although not statistically significant) of hydatid cysts of Morgagni compared with those without pain (21.1% vs 12.5 %, p = .54). Patients with infertility had a higher rate of hydatid cysts of Morgagni compared with those without infertility (38.1% vs 16.7%, p < .001), and there was a higher rate of endometriosisin the hydatid cysts of Morgagni in patients with infertility compared with those without (11.1% vs 0.0%, p < .001).

CONCLUSIONS:

This study is the first known report of endometriosis found within hydatid cysts of Morgagni. With a rate of 11.3% of cysts of Morgagni having endometriosis within them, this study supports a practice of removing hydatid cysts of Morgagni at the time of surgery in order to achieve optimal excision of endometriosis. The rates of hydatid cysts of Morgagni and of endometriosis found within hydatid cysts of Morgagni were higher in patients with infertility. Further studies are needed to evaluate whether excising cysts of Morgagni affects clinical outcomes.

 

 

J Hum Reprod Sci. 2016 Oct-Dec;9(4):250-253.

Female sexual dysfunction in patients with endometriosis: Indian scenario.

Mishra VV1Nanda S1Gandhi K1Aggarwal R1Choudhary S1Gondhali R1.

 

Abstract

BACKGROUND:

Female sexual dysfunction (FSD) in Indian women is often overlooked due to cultural beliefs and considered as social taboos. Sexuality is an important and integral part of life. There are many causes of sexual dysfunction, but the prevalence of FSD in endometriotic patients is still underdiagnosed.

MATERIALS AND METHODS:

Study design – Cross-sectional observational study conducted at tertiary care center, from June 2015 to March 2016. Sample size – Fifty-one patients in reproductive age group (18-47 years) who were diagnosed with endometriosis on diagnostic laparoscopy were included. Methods – FSD was assessed with a detailed 19-item female sexual function index questionnaire. All six domains of sexual dysfunction, i.e., desire, arousal, lubrication, orgasm, satisfaction, and pain were studied. Exclusion – Patients with other gynecological, medical or surgical history were excluded.

RESULTS:

Out of 51 patients with endometriosis, 47.06% of patients had sexual dysfunction. With the increase in staging of endometriosis, sexual dysfunction prevalence is also rising. FSD was 100% in patients with severe endometriosis as compared to 33.33% in minimal endometriosis.

CONCLUSION:

Every individual deserves good sexual life. The sexual dysfunction associated with endometriosisshould also be taken into consideration while managing these patients.

 

 

Obstet Gynecol Sci. 2017 Jan;60(1):63-68.

In vitro fertilization outcomes in women with surgery induced diminished ovarian reserve after endometrioma operation: Comparison with diminished ovarian reserve without ovarian surgery.

Hong SB1Lee NR1Kim SK2Kim H3Jee BC2Suh CS2Kim SH3Choi YM3.

 

Abstract

OBJECTIVE:

To compare the in vitro fertilization (IVF) outcomes between women with diminished ovarian reserve (DOR) after endometrioma operation and women with DOR without ovarian surgery.

METHODS:

This retrospective case-control study included 124 women aged under 40 and had DOR (serum anti-Müllerian hormone level <1.1 ng/mL or antral follicle count ≤6). They participated in fresh first and/or second IVF cycles between March in 2010 and December in 2015. Basal characteristics and IVF outcomes were compared between 47 cycles (32 women) with surgery-induced DOR and 119 cycles (92 women) with DOR without ovarian surgery.

RESULTS:

Basal characteristics were similar in both groups except that the median ages were lower in the surgery-induced DOR group compared to the DOR group without ovarian surgery. The data regarding the controlled ovarian stimulation and IVF cycle outcomes showed similar result in both groups. Also, clinical pregnancy and live birth rate were not different significantly between two groups.

CONCLUSION:

In the same condition of DOR, clinical pregnancy and live birth rate were not different significantly between two groups regarding etiology of DOR.

 

 

Chin Med J (Engl). 2017 Feb 20;130(4):428-433.

Effects of Previous Laparoscopic Surgical Diagnosis of Endometriosis on Pregnancy Outcomes.

Li H1Zhu HL2Chang XH1Li Y2Wang Y2Guan J3Cui H1.

 

Abstract

BACKGROUND:

The association between the previous history of endometriosis and obstetric outcomes is still ambiguous. This study aimed to evaluate the effects of previous history of operatively diagnosed endometriosison pregnancy outcomes.

METHODS:

A total of 98 primiparous women who had been diagnosed with endometriosis by previous laparoscopic surgery were included in this retrospective cohort study. Pregnancy outcomes were compared between these women (study group) who had a live birth and 300 women without endometriosis (control group) who had a live birth. In the study group, the pregnancy outcomes of 74 women who conceived naturally (no assisted reproductive technology [ART] subgroup) were simultaneously compared with 24 women who conceived by ART (ART subgroup).

RESULTS:

Miscarriage was observed in 23 of 98 women with endometriosis (23.5%). There were 75 women who had a live birth after laparoscopic diagnosis of endometriosis in the study group eventually. On multivariate analysis, the postpartum hemorrhage rate increased significantly in the study group when compared with the control group (adjusted odds ratio: 2.265, 95% confidence interval: 1.062, 4.872; P = 0.034). There was an upward tendency of developing other pregnancy-related complications, such as preterm birth, placental abruption, placenta previa, cesarean section, fetal distress/anemia, and others in the study group than in the control group. However, the differences showed no statistical significance. Within the study group, the occurrence rate of postpartum hemorrhage and preterm birth was both higher in the ART subgroup than in the no ART subgroup. The differences both had statistical significance (44.4% vs. 17.5%, P = 0.024 and 27.8% vs. 1.8%, P = 0.010, respectively). At the same time, median (interquartile range) for gestational age at delivery in the ART subgroup was significantly shorter than that in the no ART subgroup (38 weeks [36-39 weeks] vs. 39 weeks [38-40 weeks]; P = 0.005).

CONCLUSIONS:

Endometriosis may affect obstetric outcomes. Women with endometriosis have a higher risk of postpartum hemorrhage. Women with endometriosis who conceived by ART may have a higher risk of postpartum hemorrhage and preterm birth than those conceived naturally.

 

 

Sci Rep. 2017 Feb 20;7:42939.

Effects of U0126 and MK2206 on cell growth and re-growth of endometriotic stromal cells grown on substrates of varying stiffness.

Matsuzaki S1,2,3Pouly JL1Canis M1,2,3.

 

Abstract

Endometriosis is a common gynecological disorder responsible for infertility and pelvic pain. A complete cure for patients with endometriosis awaits new targets and strategies. Here we show that U0126 (a MEK inhibitor) and MK2206 (an AKT inhibitor) synergistically inhibit cell growth of deep endometriotic stromal cells (DES) grown on polyacrylamide gel substrates (PGS) of varying stiffness (2 or 30 kilopascal [kPa]) or plastic in vitro. No significant differences in cell proliferation were observed among DES, endometrial stromal cells of patients with endometriosis (EES) from the proliferative phase (P), EES-S (secretory phase) and EES-M (menstrual phase) compared to cells grown on a substrate of the same stiffness at both higher (U0126 [30 μM] and MK2206 [9 μM]) and lower (U0126 [15 μM] and MK2206 [4.5 μM]) combined doses. However, cell re-growth of DES after drug discontinuation was higher than that of EES-P and EES-S when cells were grown on rigid substrates at both combined doses. Combination U0126 and MK2206 treatment is more effective than each drug alone in cell growth inhibition of DES. However, further studies are required to investigate the mechanisms underlying high cell survival and proliferation after drug discontinuation for developing target therapies that prevent recurrence.

 

 

Obstet Gynecol Surv. 2017 Feb;72(2):116-122.

Diagnosis and Management of Abdominal Wall Endometriosis: A Systematic Review and Clinical Recommendations.

Rindos NB1Mansuria S2.

 

Abstract

IMPORTANCE:

Abdominal wall endometriosis (AWE) is a rare but easily treated cause of pain in women, especially those who have undergone cesarean deliveries.

OBJECTIVE:

This article reviews the diagnosis and management of AWE, a condition that generally develops after surgery but may arise spontaneously. We present a systematic review of the existing literature on AWE, as well as our clinical recommendations for medical and surgical management.

EVIDENCE ACQUISITION:

We searched PubMed and other databases using the search criteria “abdominal wall endometriosis,” “abdominal wall endometriomas,” and “abdominal wall mass.” The references of those articles were then reviewed, and additional publications were evaluated.

RESULTS:

Many case reports and case series have been published describing AWE. The overall quality of evidence is poor due to the lack of prospective studies and heterogeneous descriptions of AWE lesions and treatment options. Based on the available literature, it appears that AWE may arise spontaneously but is generally associated with prior pelvic surgery. Abdominal wall endometriosis can be diagnosed with a careful history and physical examination. Imaging including ultrasound and magnetic resonance imaging can assist with localization of the lesions, and aid in surgical excision and management. Lesions that have been removed in their entirety are unlikely to reoccur.

CONCLUSIONS AND RELEVANCE:

Although limited, the body of literature describing management of AWE suggests that it can be successfully treated in most patients with careful surgical planning.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Apr;211:108-111.

Dienogest and deep infiltrating endometriosis: The remission of symptoms is not related to endometriosis nodule remission.

Leonardo-Pinto JP1Benetti-Pinto CL1Cursino K1Yela DA2.

 

Abstract

OBJECTIVE:

To evaluate the effectiveness of dienogest in controlling pain caused by deep infiltrating endometriosis (DIE), its influence on the quality of live (QoL) of women affected by the disease, and the effect of the drug on the volume of endometriotic lesions.

STUDY DESIGN:

A prospective cohort study including 30 women with a sonographic diagnosis of DIE (intestinal and posterior fornix) treated with dienogest 2mg per day for 12 months. We evaluated the pain symptoms and the volume of the intestinal and posterior fornix lesions before and after 12 months of use of dienogest. To perform the statistical analysis, we used the Wilcoxon signed-rank test, and the relationship between the data was tested using the Spearman correlation coefficient.

RESULTS:

Women were on average 36.13±6.24years old. Pain symptoms most commonly reported were dyspareunia (83.3%), dysmenorrhea (73.3%), and pelvic pain (66.7%). After 12 months of treatment with dienogest, there was significant improvement of various symptoms (dyspareunia p=0.0093, dysmenorrhea p<0.0001; pelvic pain p=0.0007; and bowel pain p<0.0001), without a reduction in the volume of endometriotic nodules. There were significant improvements in the parameters that comprise the QoL (physical p<0.0001; p=0.0007 psychological) and the self-assessment of QoL (p=0.0069) and health (p=0.0001).

CONCLUSION:

Dienogest is an effective medication to control symptoms of pain related to DIE, even without reducing the volume of DIE nodules.

 

 

Acta Obstet Gynecol Scand. 2017 Jun;96(6):644-658

Relevant human tissue resources and laboratory models for use in endometriosis research.

Greaves E1Critchley HOD1Horne AW1Saunders PTK2.

 

Abstract

Endometriosis is characterized by the growth of endometrium-like tissue outside the uterus, most commonly on the pelvic peritoneum and ovaries. Although it may be asymptomatic in some women, in others it can cause debilitating pain, infertility or other symptoms including fatigue. Current research is directed both at understanding the complex etiology and pathophysiology of the disorder and at the development of new nonsurgical approaches to therapy that lack the unwanted side effects of current medical management. Tools for endometriosis research fall into two broad categories; patient-derived tissues, and fluids (and cells isolated from these sources) or models based on the use of cells or animals. In this review, we discuss the literature that has reported data from the use of these tools in endometriosis research and we highlight the strengths and weaknesses of each. Although many different models are reported in the literature, hypothesis-driven research will only be facilitated with careful experimental design and selection of the most appropriate human tissue from patients with and without endometriosis and combinations of physiologically relevant in vitro and in vivo laboratory models.

 

 

 

 

Gynecol Obstet Fertil Senol. 2017 Jan;45(1):15-21

Deep infiltrative endometriosis without digestive involvement, what is the impact of surgery on in vitro fertilization outcomes? A retrospective study.

Mounsambote L1Cohen J2Bendifallah S1d’Argent EM1Selleret L1Chabbert-Buffet N3Ballester M3Antoine JM1Daraï E3.

 

Abstract

OBJECTIVES:

To evaluate the impact of complete removal of endometriosis in case of deep infiltrative endometriosis without digestive involvement, on in vitro fertilization outcomes.

METHODS:

Retrospective monocentric study. We included infertile women with deep infiltrative endometriosiswithout colorectal involvement that underwent IVF. Women were divided in two groups, following their history: “surgery” when they underwent complete endometriosis resection before IVF and “without surgery” when they underwent IVF without endometriosis removal. We analysed IVF outcomes considering pregnancy rates per cycle and cumulative pregnancy rates per patient.

RESULTS:

We included 72 patients: 35 in the “surgery” group and 37 in the “without surgery” group. Women in the two groups were comparable in terms of baseline characteristics (age, body mass index, anti-Müllerian hormone, antral follicular count), endometriosis localizations and in vitro fertilization parameters. Cumulative pregnancy rates per patient were similar in both groups (40 % in the “surgery” group and 41 % in the “without surgery” group; P=1). Clinical pregnancy rate per cycle were also comparable groups (24 % in the “surgery” group and 28 % in the “without surgery” group; P=0.67). Surgery performed was comparable in women that became pregnant and in women that did not. Age was lower in women that became pregnant (P=0.01) and there were more pregnancy obtained in women under 35 years.

CONCLUSION:

In women with deep infiltrative endometriosis without digestive involvement, in vitro fertilization outcomes were not impacted by surgery. Therapeutic choice between IVF or surgery as first-line treatment remains thus questionable and shall be guided by other influencing factors, such as pain symptomatology, age, tubal permeability, ovarian reserve, partner’s sperm characteristics and woman’s choice.

 

 

 

 

Fertil Steril. 2017 Apr;107(4):996-1002

Laparoscopy vs. Robotic Surgery for Endometriosis (LAROSE): a multicenter, randomized, controlled trial.

Soto E1Luu TH2Liu X3Magrina JF4Wasson MN4Einarsson JI5Cohen SL5Falcone T6.

 

Abstract

OBJECTIVE:

To determine whether the use of the robot for surgical treatment of endometriosis is better than traditional laparoscopy in terms of operative length, perioperative parameters, and quality of life outcomes.

DESIGN:

Multicenter, randomized clinical trial.

SETTING:

University teaching hospitals.

PATIENT(S):

Women aged >18 years with suspected endometriosis who elected to undergo surgical management.

INTERVENTION(S):

Randomization to conventional or robot-assisted laparoscopic removal of endometriosis.

MAIN OUTCOME MEASURE(S):

The primary outcome measured was operative time. Secondary outcomes were perioperative complications and quality of life.

RESULT(S):

The mean operative time for robotic vs. laparoscopic surgery for endometriosis was 106.6 ± 48.4 minutes vs. 101.6 ± 63.2 minutes. There were no differences in blood loss, intraoperative or postoperative complications, or rates of conversion to laparotomy in the two arms. Both groups reported significant improvement on condition-specific quality of life outcomes at 6 weeks and 6 months.

CONCLUSION(S):

There were no differences in perioperative outcomes between robotic and conventional laparoscopy.

 

 

 

 

 

 

Fertil Steril. 2017 Apr;107(4):987-995.

Important role of collective cell migration and nerve fiber density in the development of deep nodular endometriosis.

Orellana R1García-Solares J1Donnez J2van Kerk O1Dolmans MM3Donnez O4.

 

Abstract

OBJECTIVE:

To evaluate deep nodular endometriotic lesions induced in baboons over 12 months and analyze collective cell migration and nerve fiber density.

DESIGN:

Morphologic and immunohistochemical analysis of endometriotic lesions induced in baboons over the course of 1 year.

SETTING:

Academic research unit.

ANIMAL(S):

Three female baboons (Papio anubis).

INTERVENTION(S):

Recovery of induced deep nodular endometriotic nodules from baboons.

MAIN OUTCOME MEASURE(S):

Evaluation of the morphology of glands by analysis of the center of lesions and the invasion front; immunohistochemical staining with Ki67, E-cadherin, and β-catenin for investigation of mitotic activity and cell-cell junctions, and with protein gene product 9.5 and nerve growth factor (NGF) for study of nerve fiber density (NFD).

RESULT(S):

All (100%) of the lesions were invasive 1 year after induction, compared with 42.29% after 6 months. Glands from the invasion front showed significantly reduced thickness but significantly higher mitotic activity. E-Cadherin and β-catenin expression were similar between the center and front. NFD was significantly higher in lesions induced after 1 year than after 6 months, and NGF expression was significantly lower in 1-year lesions than in 6-month lesions.

CONCLUSION(S):

Nodular endometriotic lesions induced in the baboon model were found to be significantly more invasive and innervated after 12 months than after 6 months. The invasive phenotype was highly expressed in glands at the invasion front, and our study suggests that nerve fibers play a role in the development of lesions as observed in women.

 

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